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Cryptogenic stroke accounts for 30% to 40% of ischemic stroke. It is essential to determine the possible culprit because this will improve secondary stroke prevention strategies.We performed a narrative nonsystematic review of the literature that included randomized trials, exploratory comparative studies, and case series on cryptogenic stroke.There are several possible mechanisms implicated in cryptogenic stroke, including occult paroxysmal atrial fibrillation, patent foramen ovale, aortic arch atherosclerosis, atrial cardiopathy, and substenotic atherosclerosis. The heterogeneity of these mechanisms leads to differences in stroke prevention strategies among cryptogenic stroke patients.A thorough diagnostic evaluation is essential to determine the pathogenesis in cryptogenic stroke. This approach, in addition to risk factor management and lifestyle modifications, will lead to improved stroke prevention strategies in patients with cryptogenic stroke. This will allow for targeted clinical trials to improve stroke prevention strategies in this patient population.